Post-zygotic Point Mutations

My general practice in counseling families with a child who has a suspected “de novo” dominant disorder is to estimate an approximate 5% recurrence risk for their future children based on potential gonadal mosaicism in the parents.

However, a recent paper by Acuna-Hidalgo et al (AJHG, Volume 97, Issue 1, p67–74, 2 July 2015) presented work in which they found that 6.5% of de novo mutations were actually present as mosaic mutations in the blood of the affected individual, and therefore likely happened post-zygotically.

If detection of this low level mosaicism were routinely available, this would significantly improve estimates of risk for parental gonadal mosaicism.